Transcriptional profiling has revealed that Mycobacterium tuberculosis adapts both its metabolic and respiratory states during infection, utilising lipids as a carbon source and switching to alternative electron acceptors. These global gene expression datasets may be exploited to identify virulence determinants and to screen for new targets for rational drug design. Characterising the changing physiological predicament of distinct M. tb populations during infection will help expose the fundamental biology of M. tb highlighting mechanisms that influence tuberculosis pathogenicity.